The field of the invention relates to methods for treating cancers. In particular, the field of the invention relates to methods for treating Set1B/COMPASS-associated cancers that are characterized by overexpression of Set1B/COMPASS.
Mutations and translocations within the COMPASS (Complex Proteins Associated with Set1) family of histone lysine methyltransferases are associated with a large number of human diseases including cancer. We have found that Set1B/COMPASS is overexpressed in human breast cancer and that COMPASS overexpression is significantly correlated with ER-negative patients' survival. We also have demonstrated that the depletion of Set1B selectively inhibits multiple triple negative cancer (TNBC) cell survival, but does not affect ER-positive or normal epithelia cell growth. Furthermore, we have demonstrated that the loss of Set1B or Set1B/BOD1 interactions induces activation of the AdipoR1/AMPK signaling pathway, which is hyper-inactivated in both obesity and during TNBC development. Finally, we have identified small molecular agonists for the Set1B/COMPASS target, the Adiponectin receptor 1, and demonstrated that these inhibitors effectively inhibit TNBC cells growth in vitro and in vivo.